Carcinoma of unknown primary (CUP) is a set of heterogeneous, biopsy-confirmed malignancies wherein metastatic disease presents without an identifiable primary tumor site or tissue of origin (ToO). This problem represents approximately 3-5 percent of all cancers, making it the seventh most common malignancy. The prognosis and therapeutic regimen of patients are dependent on the origin of the primary tumor, underscoring the need to identify the site of the primary tumor. A variety of methods are currently used to resolve this problem. Serum tumor Markers can be used for differential diagnosis. Although they lack adequate specificity, they can be used in combination with pathologic and clinical information. Immunohistochemical (IHC) methods can be used to identify tumor lineage but very few IHC Markers are 100 percent specific. Therefore, pathologists often use a panel of IHC Markers. Several studies have demonstrated accuracies of 66-88 percent using four to 14 IHC Markers. More expensive diagnostic workups include imaging methods such as chest x-ray, computed tomographic (CT) scans, and positron emission tomographic (PET) scans. Each of these methods can identify the primary in 30 to 50 percent of cases. Despite these sophisticated technologies, the ability to resolve CUP cases is only 20-30 percent ante mortem. A promising new approach lies in the ability of genome-wide gene expression profiling to identify the origin of tumors. In order for these expression profiling technologies to be useful in the clinical setting, two major obstacles must be overcome. First, since gene expression profiling was conducted entirely on primary tissues, gene marker candidates must be validated on metastatic tissues to confirm that their tissue specific expression is preserved in metastasis. Second, the gene expression profiling technology must be able to utilize formalin-fixed, paraffin-embedded (FFPE) tissue, since fixed tissue samples are the standard material in current practice. Formalin fixation results in degradation of the RNA so existing microarray protocols will not perform as reliably. Additionally, the profiling technology must be robust, reproducible, and easily accessible.
Accordingly, there is a need in the art for methods for the identification of the origin of a CUP which overcome the problems of the methods known in the prior art.